Vitamin D receptor-modulated Hsp70/AT1 expression may protect kidneys of SHRs at structural and functional levels

ISABEL MERCEDES GARCÍA; JONATHAN GUARESCHI; LUCIANA MAZZEI; WALTER MANUCHA

Mendoza

Otro; XXXI Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2013

Sociedad de Biología de Cuyo

Previous hypertension studies have shown that low levels of vitamin D are linked to elevated renin-angiotensin system. The heat shock protein 70 regulates signaling pathways for cellular oxidative stress responses. Hsp70 has been shown to protect against Angiotensin II-induced hypertension and exert a cytoprotective effect. Here, we wanted to evaluate whether the vitamin D receptors (VDR) associated with Hsp70/AT1 expression may be involved in the mechanism by which paricalcitol provides renal protection in spontaneously hypertensive rats (SHRs). One-month-old female SHRs were treated for 4 months with vehicle, paricalcitol, enalapril, or a combination of both paricalcitol and enalapril. The following studies were performed: blood pressure, biochemical parameters, fibrosis, apoptosis, mitochondrial morphology; and VDR/AT1 receptor and Hsp70 expressions in the renal cortex. Blood pressure was markedly reduced by enalapril or the combination but not by paricalcitol itself. However, VDR activation, by enalapril or combination, prevented fibrosis, the number of TUNEL-positive apoptotic cells, mitochondrial damage, and NADPH oxidase activity in SHRs. Additionally, high AT1 receptor expression, like low Hsp70 expression (immunohistochemical / immunofluorescence studies), were reversed in the renal cortexes of paricalcitol and/or enalapril-treated animals (SHRs), and these changes were most marked in the combined therapy group. Finally, all of the recovery parameters were consistent with an improvement in VDR expression. Data suggest that Hsp70/AT1 modulated by VDR is involved in the mechanism by which paricalcitol provides renal protection in SHRs.